Probenecid and Colchicine

WARNINGS

Exacerbation of gout following therapy with probenecid and colchicine may occur;
in such cases additional colchicine or other appropriate therapy is advisable.

Probenecid increases plasma concentrations of methotrexate in both animals
and humans. In animal studies, increased methotrexate toxicity has been reported.
If probenecid and colchicine is given with methotrexate, the dosage of methotrexate
should be reduced and serum levels may need to be monitored.

In patients on probenecid and colchicine the use of salicylates in either small
or large doses is contraindicated because it antagonizes the uricosuric action
of probenecid. The biphasic action of salicylates in the renal tubules accounts
for the so-called "paradoxical effect" of uricosuric agents. In patients
on probenecid and colchicine who require a mild analgesic agent the use of acetaminophen
rather than small doses of salicylates would be preferred.

Rarely, severe allergic reactions and anaphylaxis have been reported with the
use of probenecid and colchicine. Most of these have been reported to occur
within several hours after readministration following prior usage of the drug.

The appearance of hypersensitivity reactions requires cessation of therapy
with probenecid and colchicine.

Colchicine has been reported to adversely affect spermatogenesis in animals.
Reversible azoospermia has been reported in one patient.

PRECAUTIONS

General

Hematuria, renal colic, costovertebral pain, and formation of uric acid stones
associated with the use of probenecid and colchicine in gouty patients may be
prevented by alkalization of the urine and a liberal fluid intake (see DOSAGE
AND ADMlNlSTRATION). In these cases when alkali is administered, the
acid-base balance of the patient should be watched.

Probenecid and colchicines has been used in patients with some renal impairment
but dosage requirements may be increased. Probenecid and colchicine may not
be effective in chronic renal insufficiency particularly when the glomerular
filtration rate is 30 mL/minute or less.

A reducing substance may appear in the urine of patients receiving probenecid.
This disappears with discontinuance of therapy. Suspected glycosuria should
be confirmed by using a test specific for glucose.

Adequate animal studies have not been conducted to determine the carcinogenicity
potential of probenecid or this drug combination. Since colchicines is an established
mutagen, its ability to act as a carcinogen must be suspected and administration
of probenecid and colchicine should involve a weighing of the benefit-vs-risk
when long-term administration is contemplated.

Last reviewed on RxList: 9/29/2008
This monograph has been modified to include the generic and brand name in many instances.